tbuckley/cabot-search huggingface dataset:
Helen Salisbury: Where have our GPs gone?
Authors: Helen Salisbury
Journal: BMJ (2022)

That question topped the 3 May front page of the Daily Mail-a tabloid newspaper not known for its support of our profession.It was followed by an article outlining the 10.5% rise in registered patients per GP since 2017. 1 Each GP now has an average of 2217 patients, up from 2007 patients five years ago, although these numbers hide huge variation.In the worst hit areas each GP is responsible for the care of 3000 patients.It's difficult to know how this ratio can be safe.
Complex Persistent Benzodiazepine Dependence—When Benzodiazepine Deprescribing Goes Awry
Authors: Linda Peng, Thomas W. Meeks, Christopher K. Blazes
Journal: JAMA Psychiatry (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection
Authors: Chengzi I. Kaku, Alan J. Bergeron, Clas Ahlm, Johan Normark, Mrunal Sakharkar, Mattias N. E. Forsell, Laura M. Walker
Journal: Science Immunology (2022)

Understanding immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)–specific B cell responses after Omicron/BA.1 infection in messenger RNA–vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells. BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit, which is highly conserved across SARS-CoV-2 variants of concern (VOCs), and toward the antigenically variable receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 VOCs. Together, these findings provide insights into the role of preexisting immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.
Effect of a Novel Intervention Targeting Appetitive Traits on Body Mass Index Among Adults With Overweight or Obesity
Authors: Kerri N. Boutelle, Dawn M. Eichen, Carol B. Peterson, David R. Strong, Dong-Jin Eastern Kang-Sim, Cheryl L. Rock, Bess H. Marcus
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Behavioral weight loss (BWL) programs result in weight loss for some, but most individuals regain the weight. The behavioral susceptibility theory proposes that genetically determined appetitive traits, such as food responsiveness (FR) and satiety responsiveness (SR), interact with the environment and lead to overeating and weight gain; the regulation of cues (ROC) intervention was developed specifically to target FR and SR. <h3>Objective</h3> To evaluate the efficacy of ROC, ROC combined with BWL (ROC+), BWL, and an active comparator (AC) over 12 months of treatment and 12 months of follow-up. <h3>Design, Setting, and Participants</h3> This randomized clinical trial was conducted from December 2015 to December 2019 in a university clinic. A total of 1488 volunteers from the community inquired about the study; 1217 were excluded or declined to participate. Eligibility criteria included body mass index (BMI) of 25 to 45, age 18 to 65 years, and lack of comorbidities or other exclusionary criteria that would interfere with participation. Data were analyzed from September 2021 to January 2022. <h3>Interventions</h3> ROC uniquely targeted FR and SR. BWL included energy restriction, increasing physical activity, and behavior therapy techniques. ROC+ combined ROC with BWL. AC included mindfulness, social support, and nutrition education. <h3>Main Outcomes and Measures</h3> Change in body weight as measured by BMI. <h3>Results</h3> A total of 271 adults (mean [SD] age, 46.97 [11.80] years; 81.6% female [221 participants]; mean [SD] BMI, 34.59 [5.28]; 61.9% White [167 participants]) were assessed at baseline, midtreatment, posttreatment, and 6-month and 12-month follow-up. Sixty-six participants were randomized to AC, 69 to ROC, 67 to ROC+, and 69 to BWL. Results showed that ROC, ROC+, and BWL interventions resulted in significantly lower BMI at the end of treatment (BMI ROC, −1.18; 95% CI, −2.10 to −0.35; BMI ROC+, −1.56; 95% CI, −2.43 to -0.67; BMI BWL, −1.58; 95% CI, −2.45 to −0.71). Compared with BWL, BMI at the end of treatment was not significantly different from ROC or ROC+ (BMI ROC, 0.40; 95% CI, −0.55 to 1.36; BMI ROC+, 0.03; 95% CI, −0.88 to 0.93); however, the BMI of the AC group was substantially higher (BMI AC, 1.58; 95% CI, 0.72 to 2.45). BMI reductions at 24 months after randomization were similar for ROC, ROC+, and BWL. Importantly, FR was a moderator of treatment effects with more weight loss for participants who scored higher in FR in the ROC and ROC+ groups. <h3>Conclusions and Relevance</h3> These findings suggest that ROC and ROC+ provide alternative weight loss approaches for adults. These models could be particularly effective for individuals who struggle with FR and could be used as a precision approach for weight loss. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02516839
Recent Progress in Microneedles‐Mediated Diagnosis, Therapy, and Theranostic Systems (Adv. Healthcare Mater. 10/2022)
Authors: Jian Yang, Jingbo Yang, Xia Gong, Ying Zheng, Shengzhu Yi, Yanxiang Cheng, Yanjun Li, Bin Liu, Xi Xie, Changqing Yi, Lelun Jiang
Journal: Advanced Healthcare Materials (2022)
Transcriptional Repression by FoxM1 Suppresses Tumor Differentiation and Promotes Metastasis of Breast Cancer
Authors: Dragana Kopanja, Vaibhav Chand, Eilidh O'Brien, Nishit K. Mukhopadhyay, Maria P. Zappia, Abul B.M.M.K. Islam, Maxim V. Frolov, Bradley J. Merrill, Pradip Raychaudhuri
Journal: Cancer Research (2022)

The transcription factor Forkhead box M1 (FoxM1) is overexpressed in breast cancers and correlates with poor prognosis. Mechanistically, FoxM1 associates with CBP to activate transcription and with Rb to repress transcription. Although the activating function of FoxM1 in breast cancer has been well documented, the significance of its repressive activity is poorly understood. Using CRISPR–Cas9 engineering, we generated a mouse model that expresses FoxM1-harboring point mutations that block binding to Rb while retaining its ability to bind CBP. Unlike FoxM1-null mice, mice harboring Rb-binding mutant FoxM1 did not exhibit significant developmental defects. The mutant mouse line developed PyMT-driven mammary tumors that were deficient in lung metastasis, which was tumor cell-intrinsic. Single-cell RNA-seq of the tumors revealed a deficiency in prometastatic tumor cells and an expansion of differentiated alveolar type tumor cells, and further investigation identified that loss of the FoxM1/Rb interaction caused enhancement of the mammary alveolar differentiation program. The FoxM1 mutant tumors also showed increased Pten expression, and FoxM1/Rb was found to activate Akt signaling by repressing Pten. In human breast cancers, expression of FoxM1 negatively correlated with Pten mRNA. Furthermore, the lack of tumor-infiltrating cells in FoxM1 mutant tumors appeared related to decreases in pro-metastatic tumor cells that express factors required for infiltration. These observations demonstrate that the FoxM1/Rb-regulated transcriptome is critical for the plasticity of breast cancer cells that drive metastasis, identifying a prometastatic role of Rb when bound to FoxM1.
Comparison of laparoscopic versus open radical antegrade modular pancreatosplenectomy for pancreatic cancer: A systematic review and meta-analysis
Authors: Wei Tang, Yu-Fei Zhang, Yu-Fei Zhao, Xu-Fu Wei, Heng Xiao, Qiao Wu, Cheng-You Du, Jian-Guo Qiu
Journal: International Journal of Surgery (2022)
Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study
Authors: Rafael Cardoso, Feng Guo, Thomas Heisser, Harlinde De Schutter, Nancy Van Damme, Mef Christina Nilbert, Anne Julie Tybjerg, Anne-Marie Bouvier, Véronique Bouvier, Guy Launoy, Anne-Sophie Woronoff, Mélanie Cariou, Michel Robaszkiewicz, Patricia Delafosse, Florence Poncet, Paul M Walsh, Carlo Senore, Stefano Rosso, Valery E P P Lemmens, Marloes A G Elferink, Sonja Tomšič, Tina Žagar, Arantza Lopez de Munain Marques, Rafael Marcos-Gragera, Montse Puigdemont, Jaume Galceran, Marià Carulla, Antonia Sánchez-Gil, María-Dolores Chirlaque, Michael Hoffmeister, Hermann Brenner
Journal: The Lancet. Gastroenterology & hepatology (2022)
Gastrointestinal neoplasia: carcinogenic interaction between bile acids and Helicobacter pylori in the stomach
Authors: Madeline Alizadeh, Jean-Pierre Raufman
Journal: Journal of Clinical Investigation (2022)

Bile acids modulate cell functions in health and disease, however, the mechanisms underlying their actions on neoplastic cells in the gastrointestinal (GI) tract remain largely unknown. In this issue of the JCI, Noto et al. comprehensively analyzed how interactions between Helicobacter pylori infection, iron deficiency, and bile acids modulate gastric inflammation and carcinogenesis. The investigators used sophisticated models, including INS-GAS mice with elevated serum gastrin and gastric acid secretion, in which H. pylori infection mimics human disease progression, to show that selected bile acids potentiated the carcinogenic effects of H. pylori infection and iron depletion. This elegant work has broad translational implications for microbe-associated GI neoplasia. Importantly, bile acid sequestration robustly attenuated the combined effects of H. pylori infection and iron depletion on gastric inflammation and cancer.
Targeting the hepatitis B cccDNA with a sequence-specific ARCUS nuclease to eliminate hepatitis B virus in vivo
Authors: Cassandra L. Gorsuch, Paige Nemec, Mei Yu, Simin Xu, Dong Han, Jeff Smith, Janel Lape, Nicholas van Buuren, Ricardo Ramirez, Robert C. Muench, Meghan M. Holdorf, Becket Feierbach, Greg Falls, Jason Holt, Wendy Shoop, Emma Sevigny, Forrest Karriker, Robert V. Brown, Amod Joshi, Tyler Goodwin, Ying K. Tam, Paulo J.C. Lin, Sean C. Semple, Neil Leatherbury, William E. Delaney IV, Derek Jantz, Amy Rhoden Smith
Journal: Molecular Therapy (2022)

Persistence of chronic hepatitis B (CHB) is attributed to maintenance of the intrahepatic pool of the viral covalently closed circular DNA (cccDNA), which serves as the transcriptional template for all viral gene products required for replication. Current nucleos(t)ide therapies for CHB prevent virus production and spread but have no direct impact on cccDNA or expression of viral genes. We describe a potential curative approach using a highly specific engineered ARCUS nuclease (ARCUS-POL) targeting the hepatitis B virus (HBV) genome. Transient ARCUS-POL expression in HBV-infected primary human hepatocytes produced substantial reductions in both cccDNA and hepatitis B surface antigen (HBsAg). To evaluate ARCUS-POL in vivo, we developed episomal adeno-associated virus (AAV) mouse and non-human primate (NHP) models containing a portion of the HBV genome serving as a surrogate for cccDNA. Clinically relevant delivery was achieved through systemic administration of lipid nanoparticles containing ARCUS-POL mRNA. In both mouse and NHP, we observed a significant decrease in total AAV copy number and high on-target indel frequency. In the case of the mouse model, which supports HBsAg expression, circulating surface antigen was durably reduced by 96%. Together, these data support a gene-editing approach for elimination of cccDNA toward an HBV cure.
Multiomics identifies the link between intratumor steatosis and the exhausted tumor immune microenvironment in hepatocellular carcinoma
Authors: Hiroki Murai, Takahiro Kodama, Kazuki Maesaka, Shoichiro Tange, Daisuke Motooka, Yutaka Suzuki, Yasuyuki Shigematsu, Kentaro Inamura, Yoshihiro Mise, Akio Saiura, Yoshihiro Ono, Yu Takahashi, Yota Kawasaki, Satoshi Iino, Shogo Kobayashi, Masashi Idogawa, Takashi Tokino, Tomomi Hashidate‐Yoshida, Hideo Shindou, Masanori Miyazaki, Yasuharu Imai, Satoshi Tanaka, Eiji Mita, Kazuyoshi Ohkawa, Hayato Hikita, Ryotaro Sakamori, Tomohide Tatsumi, Hidetoshi Eguchi, Eiichi Morii, Tetsuo Takehara
Journal: Hepatology (2022)

Background and Aims: Immunotherapy has become the standard‐of‐care treatment for hepatocellular carcinoma (HCC), but its efficacy remains limited. To identify immunotherapy‐susceptible HCC, we profiled the molecular abnormalities and tumor immune microenvironment (TIME) of rapidly increasing nonviral HCC. Approaches and Results: We performed RNA‐seq of tumor tissues in 113 patients with nonviral HCC and cancer genome sequencing of 69 genes with recurrent genetic alterations reported in HCC. Unsupervised hierarchical clustering classified nonviral HCCs into three molecular classes (Class I, II, III), which stratified patient prognosis. Class I, with the poorest prognosis, was associated with TP53 mutations, whereas class III, with the best prognosis, was associated with cadherin‐associated protein beta 1 (CTNNB1) mutations. Thirty‐eight percent of nonviral HCC was defined as an immune class characterized by a high frequency of intratumoral steatosis and a low frequency of CTNNB1 mutations. Steatotic HCC, which accounts for 23% of nonviral HCC cases, presented an immune‐enriched but immune‐exhausted TIME characterized by T cell exhaustion, M2 macrophage and cancer‐associated fibroblast (CAF) infiltration, high PD‐L1 expression, and TGF‐β signaling activation. Spatial transcriptome analysis suggested that M2 macrophages and CAFs may be in close proximity to exhausted CD8+ T cells in steatotic HCC. An in vitro study showed that palmitic acid‐induced lipid accumulation in HCC cells upregulated PD‐L1 expression and promoted immunosuppressive phenotypes of cocultured macrophages and fibroblasts. Patients with steatotic HCC, confirmed by chemical‐shift MR imaging, had significantly longer PFS with combined immunotherapy using anti–PD‐L1 and anti‐VEGF antibodies. Conclusions: Multiomics stratified nonviral HCCs according to prognosis or TIME. We identified the link between intratumoral steatosis and immune‐exhausted immunotherapy‐susceptible TIME.
Evolution and Prognostic Impact of Cardiac Damage After Aortic Valve Replacement
Authors: Philippe Généreux, Philippe Pibarot, Björn Redfors, Jeroen J. Bax, Yanglu Zhao, Raj R. Makkar, Samir Kapadia, Vinod H. Thourani, Michael J. Mack, Tamim M. Nazif, Brian R. Lindman, Vasilis Babaliaros, Flavien Vincent, Mark Russo, James M. McCabe, Linda D. Gillam, Maria C. Alu, Rebecca T. Hahn, John G. Webb, Martin B. Leon, David J. Cohen
Journal: Journal of the American College of Cardiology (2022)
Transjugular intrahepatic portosystemic shunt with or without gastro-oesophageal variceal embolisation for the prevention of variceal rebleeding: a randomised controlled trial
Authors: Yong Lv, Hui Chen, Bohan Luo, Wei Bai, Kai Li, Zhengyu Wang, Dongdong Xia, Wengang Guo, Qiuhe Wang, Xiaomei Li, Jie Yuan, Hongwei Cai, Jielai Xia, Zhanxin Yin, Daiming Fan, Guohong Han
Journal: The Lancet. Gastroenterology & hepatology (2022)
Impact of bacterial infections and spontaneous bacterial peritonitis prophylaxis on phage‐bacterial dynamics in cirrhosis
Authors: Jasmohan S. Bajaj, Marcela Peňa Rodriguez, Andrew Fagan, Sara McGeorge, Richard K. Sterling, Hannah Lee, Velimir Luketic, Michael Fuchs, Brian C. Davis, Masoumeh Sikaroodi, Patrick M. Gillevet
Journal: Hepatology (2022)

Abstract Background and Aims Gut microbiota, including bacteria and phages, are altered in cirrhosis, but their role during infections and spontaneous bacterial peritonitis (SBP) prophylaxis is unclear. Our aim was determine metagenomic changes in gut bacteria; phages and their linkages centered around Gram‐negative and Gram‐positive pathobionts in patients with cirrhosis with/without infections or SBP prophylaxis. Approach and Results We included uninfected ( n = 231) and infected ( n = 30, SBP n = 19 and urinary tract infection n = 11 before antibiotics) patients who gave stool for bacterial and phage metagenomics. We matched uninfected to infected patients 1:1 on a model for end‐stage liver disease (MELD). We also analyzed subgroups of patients with ascites matched on an MELD ( n = 73) to patients on SBP prophylaxis ( n = 7) and then to SBP infection. Phage and bacterial taxa differences (DESeq2) and correlation networks centered around Escherichia coli and Enterococcus faecium were analyzed. Infections were mostly due to Enterobacteriaceae and Enterococcus spp. On metagenomics, higher fold changes of Enterobacteriaceae members, Enterococcus and Streptococcus spp., and Escherichia phages were seen in infected patients. Correlation networks showed more complex bacteria‐phage linkages in infected patients compared with uninfected ones overall and centered around E. coli and E. faecium . SBP prophylaxis induced higher Gram‐positive bacteria. In SBP, Enterococcus and Escherichia were higher versus ascites. Correlation networks around E. coli were complex in ascites but sparse with SBP prophylaxis, whereas the reverse was seen with E. faecium . Lytic phages and those associated with antibiotic resistance were correlated with E. faecium . Conclusion In cirrhosis, there are significant changes in phage‐bacterial linkages in infected patients and those on SBP prophylaxis compared to the remaining patients. SBP prophylaxis enriches complexity of E. faecium –centered but induces a collapse in E. coli –centered phage‐bacterial correlations.
Surely not all experimental studies of bias need abandoning?
Authors: Fiona A. White
Journal: Behavioral and Brain Sciences (2022)

Cesario misrepresents experimental social psychology. The discipline encompasses significantly more than implicit bias research, including controlled decision making and real-world behavioral observations. Paradoxically, while critiquing popular implicit bias tasks, Cesario also describes task refinements that have significantly advanced their external validity and our contextual understanding of bias. Thus rather than abandonment, a call for "continued improvement" is a far more sensible proposition.
Complementary roles of surgery and systemic treatment in clear cell renal cell carcinoma
Authors: Alexandre Ingels, Riccardo Campi, Umberto Capitanio, Daniele Amparore, Riccardo Bertolo, Umberto Carbonara, Selcuk Erdem, Önder Kara, Tobias Klatte, Maximilian C. Kriegmair, Michele Marchioni, Maria C. Mir, Idir Ouzaïd, Nicola Pavan, Angela Pecoraro, Eduard Roussel, Alexandre de la Taille
Journal: Nature Reviews Urology (2022)
Moderate Hypothermia vs Normothermia and 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial ECMO
Authors: Tatsuki Uemura
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Therapeutic Targeting of the Respiratory Microbiome
Authors: Sanjay H. Chotirmall, Debby Bogaert, James D. Chalmers, Michael J. Cox, Philip M. Hansbro, Yvonne J. Huang, Philip L. Molyneaux, David N. O’Dwyer, Alexa A. Pragman, Geraint B. Rogers, Leopoldo N. Segal, Robert P. Dickson
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Therapeutic Targeting of the Respiratory Microbiome." American Journal of Respiratory and Critical Care Medicine, 206(5), pp. 535–544
Artificial intelligence in medicine: Overcoming or recapitulating structural challenges to improving patient care?
Authors: Alex John London
Journal: Cell Reports Medicine (2022)

There is considerable enthusiasm about the prospect that artificial intelligence (AI) will help to improve the safety and efficacy of health services and the efficiency of health systems. To realize this potential, however, AI systems will have to overcome structural problems in the culture and practice of medicine and the organization of health systems that impact the data from which AI models are built, the environments into which they will be deployed, and the practices and incentives that structure their development. This perspective elaborates on some of these structural challenges and provides recommendations to address potential shortcomings.
Visualising harms: barely scratching the surface
Authors: Will Stahl-Timmins
Journal: BMJ (2022)

Visualising harms: barely scratching the surface Will Stahl-Timmins data graphics designer Good visuals and graphs can quickly convey substance in a way that words cannot.Graphics make a lasting impression, are easy to digest, but hard to make.Far from being just an additional eye-catching "surface" on top of a paper, they are an integral part of how science is explained.Often, not enough attention is paid to the visual element of science communication and why it matters.I was recently involved in a project, led by Rachel Phillips, and colleagues at Imperial College London and several other UK medical schools.The project aimed to recommend graph types for reporting harms data in clinical trials.However, while we collated a few simple and easy to make graph types, the surface of this topic has barely been scratched.We need to develop and use more innovative techniques that can present data in more complex trial designs such as those with multiple outcomes and subgroups.